Design, Synthesis, and In Vitro and In Silico Biological Exploration of Novel Pyridine‐Embedded 1,3,4‐Oxadiazole Hybrids as Potential Antimicrobial Agents
Journal of Chemistry,
Год журнала:
2025,
Номер
2025(1)
Опубликована: Янв. 1, 2025
Antibiotic
resistance
represents
a
significant
public
health
challenge
in
the
current
century.
The
β‐lactam
antibiotics,
together
with
carbapenems,
are
inactivated
by
zinc‐dependent
bacterial
enzymes
called
metallo‐β‐lactamases
(MBLs).
Presently
there
no
clinically
permitted
MBL
inhibitors,
and
to
produce
such
drugs,
it
is
indispensable
comprehend
their
inhibitory
action.
We
investigated
an
efficient
synthesis
of
pyridine‐embedded
1,3,4‐oxadiazole
hybrids
(3a-c)
antimicrobial
activity
against
different
microbial
strains.
compounds
were
characterized
spectral
techniques
(viz.,
IR,
NMR,
mass).
vitro
antibacterial
antifungal
was
also
performed;
displayed
excellent
activity.
silico
docking
studies
evaluated
proteins
New
Delhi
Metallo-Beta-lactamase-1
(NDM‐1)
Mycobacterium
tuberculosis
enoyl
reductase
(INHA).
All
demonstrated
binding
affinity
for
docked
proteins.
Additionally,
molecular
dynamics
disclosed
(4a-c)
.
Язык: Английский
A decade of research effort in synthesis, biological activity assessments, and mechanistic investigations of sulfamethazine‐incorporating molecules
Archiv der Pharmazie,
Год журнала:
2025,
Номер
358(3)
Опубликована: Март 1, 2025
Abstract
Because
of
its
importance
in
medicinal
chemistry,
scientific
researchers
have
been
interested
incorporating
sulfamethazine
developing
biologically
active
candidates.
To
achieve
this,
several
synthetic
approaches
adopted.
The
adopted
included
condensation
with
electrophilic
reactants,
coupling
nucleophilic
aromatics
and
methylene
compounds,
Knoevenagel
condensation,
Doebner
Miller
reaction,
microwave‐assisted
click
cycloaddition,
green
reaction
routes,
multicomponent
reaction.
Linking
this
molecular
scaffold
to
a
variety
heterocycles
the
last
10
years
furnished
set
potential
anti‐inflammatory,
antiviral,
anticancer,
antiparkinsonian,
neuroprotective,
antidiabetic
candidates
targeting
H5N1
NA,
epidermal
growth
factor
receptor,
acetylcholinesterase
(AChE),
butylcholinesterase
(BChE),
human
carbonic
anhydrase
(
h
CA),
α‐amylase,
α‐glucosidase.
This
review
reports
all
approaches,
biological
activities
studied,
structure‐activity
relationship
analyses,
mechanistic
investigations
reported
organic
sulfamethazine‐incorporating
molecules
throughout
2015–2024,
based
on
information
retrieved
from
three
search
engines:
Scopus,
PubMed,
Google
Scholar.
Язык: Английский
Naturally occurring plant-derived sulfonated and sulfated saponins from 1983 to 2024
Medicinal Chemistry Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 19, 2025
Язык: Английский
Exploring the Potential of New Benzamide-Acetamide Pharmacophore Containing Sulfonamide as Urease Inhibitors: Structure–Activity Relationship, Kinetics Mechanism, and In Silico Studies
ACS Omega,
Год журнала:
2023,
Номер
8(48), С. 46165 - 46181
Опубликована: Ноя. 22, 2023
The
search
for
novel
drug
scaffolds
that
can
improve
effectiveness
and
safety
through
conjugates
is
a
promising
approach.
Consequently,
constitute
dynamic
field
of
study
advancement
within
medicinal
chemistry.
This
research
demonstrates
the
conjugation
diclofenac
mefenamic
acid
with
sulfa
drugs
their
screening
urease
inhibition.
These
conjugates'
structural
confirmation
was
performed
using
elemental
analysis
spectroscopic
methods,
including
IR,
1H
NMR,
13C
NMR.
Diclofenac
conjugated
sulfanilamide
(4),
sulfacetamide
(10),
(12),
sulfamethoxazole
(17)
found
potent
demonstrated
inhibition
competitively,
IC50
(μM)
values
3.59
±
0.07,
5.49
0.34,
7.92
0.27,
8.35
0.26,
respectively.
sulfathiazole
(6),
sulfamerazine
(8),
sulfaguanidine
(11),
while
sulfisoxazole
(13),
(14),
sulfadiazine
(15)
exhibited
mixed
mode
were
16.19
0.21,
9.50
0.28,
4.35
0.23,
15.86
0.25,
14.80
Furthermore,
molecular
docking
studies
employed
to
predict
binding
pose
competitive
inhibitors
at
active
site.
generated
stable
complexes
protein
observed
dynamics
(MD)
simulations,
where
no
conformational
changes
occurred
throughout
simulations.
results
highlight
potential
approved
therapeutic
molecule
give
rise
new
categories
pharmacological
agents
similarity
sulfonamides
urea
allows
them
compete
site
enzyme.
Sulfonamides
nonsteroidal
anti-inflammatory
(NSAIDs)
interact
hydrophobically
enzyme,
which
may
disturb
its
structure
catalytic
activity.
Therefore,
these
be
helpful
in
development
treatment
variety
illnesses
enzyme
involved.
Язык: Английский
The role of the sulfaguanidine molecular scaffold in drug design and development
Archiv der Pharmazie,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 10, 2024
Abstract
Developing
new
molecular
entities
is
one
of
the
most
emerging
research
areas
in
field
Medicinal
Chemistry.
Over
past
few
years,
rigorous
has
been
conducted
on
sulfaguanidine‐linked
synthetic
molecules
because
their
promising
potential
several
biological
activities.
Sulfaguanidine
actively
incorporated
design
anticancer,
antimicrobial,
antidiabetic,
antiparkinsonian,
anti‐inflammatory,
and
antiviral
candidates.
The
construction
these
effective
candidates
adopted
many
chemical
approaches.
A
number
prepared
compounds
displayed
results
that
merit
further
investigations
for
development
medications.
This
review
summarizes
different
strategies
reported
activities
throughout
2020–2024.
Язык: Английский
Novel coumarin-based acetohydrazide-1,2,3-triazole derivatives as urease enzyme inhibitors: synthesis, in vitro evaluation, and molecular dynamics simulation studies
Hassan Sepehrmansourie,
Mohammad Reza Azimi,
Ahmad Ebadi
и другие.
Heliyon,
Год журнала:
2024,
Номер
11(1), С. e41321 - e41321
Опубликована: Дек. 18, 2024
Язык: Английский
Acetylsalicylic acid-sulfa drugs conjugates as potential urease inhibitors and anti-inflammatory agents: bio-oriented drug synthesis, molecular docking, and dynamics simulation studies
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2023,
Номер
42(18), С. 9373 - 9387
Опубликована: Авг. 29, 2023
AbstractTo
explore
the
new
mode
of
action
and
reduce
side
effects,
making
conjugates
existing
drugs
is
becoming
an
attractive
tool
in
realm
medicinal
chemistry.
In
this
work,
we
exploited
approach
synthesized
to
assess
their
activities
against
enzymes
involved
different
pathological
conditions.
Specifically,
design
involving
acetylsalicylic
acid
sulfa
drugs,
validating
newly
crafted
using
techniques
like
IR,
1HNMR,
13CNMR,
elemental
analysis.
These
underwent
assessment
for
ability
inhibit
cyclooxygenase-2
(COX-2),
urease
enzymes,
anti-inflammatory
potential.
A
competitive
inhibition
was
observed
conjugated
with
sulfanilamide,
sulfacetamide,
sulfadiazine
IC50
2.49
±
0.35
µM,
6.21
0.28
6.57
0.44
respectively.
Remarkably,
acid-sulfamethoxazole
conjugate
exhibited
exceptional
activity,
effectively
curtailing
induced
edema
by
83.7%,
a
result
akin
reference
drug
indomethacin's
performance
(86.8%).
Additionally,
it
demonstrated
comparable
COX-2
(75.8%)
selective
inhibitor
celecoxib
that
77.1%
at
10
µM
concentration.
To
deepen
our
understanding,
employed
molecular
docking
predict
binding
interactions
inhibitors
receptors.
MD
simulations
were
carried
out,
confirming
stability
inhibitor-target
complexes
throughout
simulation
period,
devoid
significant
conformational
changes.
Collectively,
research
underscores
potential
coupling
approved
compounds
usher
novel
categories
pharmacological
agents,
holding
promise
addressing
wide
spectrum
disorders
enzymes.Communicated
Ramaswamy
H.
SarmaKeywords:
NSAIDssulfonamidesinflammationcyclooxygenase-2ureasemolecular
Authors'
contributionsSaghir
Ahmad:
Methodology,
Formal
analysis,
Synthesis,
Muhammad
Abdul
Qadir:
Supervision,
Research
Design,
Mahmood
Ahmed:
Review
&
editing,
Writing
-
original
draft,
Imran:
Review,
Numan
Yousaf:
Docking,
Asnuzilawati
Asari:
Hameed:
Validation
data,
Muddassar:
Docking
Simulation.Disclosure
statementThe
authors
declare
no
conflict
interest.Ethical
statementAll
animal
experimental
methods
conducted
as
per
guidelines
UK
Animals
(Scientific
Procedures)
Act
1986,
Animal
Ethical
Committee
The
University
Punjab,
Lahore-Pakistan.
albino
mice
either
sex
kept
under
standard
conditions
house,
EEC
Directive
1986
(86/609/EEC)
use
laboratory
animals
(NIH
Publication
No.
80-23;
revised
1978).Additional
informationFundingThe
received
specific
funding
work.
Язык: Английский
Jack bean urease inhibition by different root fractions of Cleome gynandra L – Kinetic mechanism and computational molecular modelling
Industrial Crops and Products,
Год журнала:
2024,
Номер
222, С. 119514 - 119514
Опубликована: Авг. 31, 2024
Язык: Английский
Clodronic Acid has Strong Inhibitory Interactions with the Urease Enzyme of Helicobacter Pylori: Computer-aided Design and in vitro Confirmation
Current Computer - Aided Drug Design,
Год журнала:
2023,
Номер
20(7), С. 1100 - 1112
Опубликована: Ноя. 14, 2023
Background:
Helicobacter
Pylori
(HP)
infection
could
lead
to
various
gastrointestinal
diseases.
Urease
is
the
most
important
virulence
factor
of
HP.
It
protects
bacterium
against
gastric
acid.
Objective:
Therefore,
we
aimed
design
urease
inhibitors
as
drugs
HP
infection.
Methods:
The
DrugBank-approved
library
was
assigned
with
3D
conformations
and
structure
prepared.
Using
a
re-docking
strategy,
proper
settings
were
determined
for
docking
by
PyRx
GOLD
software.
Virtual
screening
performed
select
best
inhibitory
based
on
binding
affinity,
FitnessScore,
orientation
critical
amino
acids
active
site.
drug
then
evaluated
IC50
diameter
zone
inhibition
bacterial
growth.
Results:
structures
prepared
screened
using
settings.
Clodronic
acid
be
best-identified
drug,
due
higher
energy,
better
interaction
urease.
In
vitro
results
also
in
line
computational
data.
values
Acetohydroxamic
Acid
(AHA)
29.78
±
1.13
47.29
2.06
μg/ml,
respectively.
Diameters
zones
18
15
mm
AHA,
Conclusion:
has
potential
than
AHA.
Given
its
approved
status,
development
repurposed
would
require
less
time
cost.
Further,
vivo
studies
unveil
efficacy
inhibitor.
Язык: Английский